The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model

Abstract

AbstractObjectiveMigraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA‐induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene–related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP‐25 through western blot analysis to gain insights into the mechanistic action of BoNT/A.MethodsBoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post‐inflammation, and alterations in CGRP release were evaluated. Changes in SNAP‐25 levels were determined using western blot analysis.ResultsUpon CFA‐induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP‐25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A‐treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release.ConclusionOur investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP‐25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.